RGD Reference Report - Expression of the skeletal muscle dystrophin-dystroglycan complex and syntrophin-nitric oxide synthase complex is severely affected in the type 2 diabetic Goto-Kakizaki rat. - Rat Genome Database

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Expression of the skeletal muscle dystrophin-dystroglycan complex and syntrophin-nitric oxide synthase complex is severely affected in the type 2 diabetic Goto-Kakizaki rat.

Authors: Mulvey, C  Harno, E  Keenan, A  Ohlendieck, K 
Citation: Mulvey C, etal., Eur J Cell Biol. 2005 Nov;84(11):867-83.
RGD ID: 1581689
Pubmed: PMID:16323284   (View Abstract at PubMed)
DOI: DOI:10.1016/j.ejcb.2005.06.007   (Journal Full-text)

The inability of insulin to stimulate glucose metabolism in skeletal muscle fibres is a classic characteristic of type 2 diabetes. Using the non-obese Goto-Kakizaki rat as an established animal model of this type of diabetes, sucrose gradient centrifugation studies were performed and confirmed the abnormal subcellular location of the glucose transporter GLUT4. In addition, this analysis revealed an unexpected drastic reduction in the surface membrane marker beta-dystroglycan, a dystrophin-associated glycoprotein. Based on this finding, a comprehensive immunoblotting survey was conducted which showed a dramatic decrease in the Dp427 isoform of dystrophin and the alpha/beta-dystroglycan subcomplex, but not in laminin, sarcoglycans, dystrobrevin, and excitation-contraction-relaxation cycle elements. Thus, the backbone of the trans-sarcolemmal linkage between the extracellular matrix and the actin membrane cytoskeleton might be structurally impaired in diabetic fibres. Immunohistochemical studies revealed that the reduction in the dystrophin-dystroglycan complex does not induce obvious signs of muscle pathology, and is neither universal in all fibres, nor fibre-type specific. Most importantly, the expression of alpha-syntrophin and the syntrophin-associated neuronal isoform of nitric oxide synthase, nNOS, was demonstrated to be severely reduced in diabetic fibres. The loss of the dystrophin-dystroglycan complex and the syntrophin-nNOS complex in selected fibres suggests a weakening of the sarcolemma, abnormal signalling and probably a decreased cytoprotective mechanism in diabetes. Impaired anchoring of the cortical actin cytoskeleton via dystrophin might interfere with the proper recruitment of the glucose transporter to the surface membrane, following stimulation by insulin or muscle contraction. This may, at least partially, be responsible for the insulin resistance in diabetic skeletal muscles.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 2 diabetes mellitus  ISODag1 (Rattus norvegicus)1581689; 1581689protein:decreased expression:skeletal muscleRGD 
type 2 diabetes mellitus  IEP 1581689protein:decreased expression:skeletal muscleRGD 
type 2 diabetes mellitus  ISONos1 (Rattus norvegicus)1581689; 1581689 RGD 
type 2 diabetes mellitus  IEP 1581689 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dag1  (dystroglycan 1)
Nos1  (nitric oxide synthase 1)

Genes (Mus musculus)
Dag1  (dystroglycan 1)
Nos1  (nitric oxide synthase 1, neuronal)

Genes (Homo sapiens)
DAG1  (dystroglycan 1)
NOS1  (nitric oxide synthase 1)

Objects referenced in this article
Gene Dtna dystrobrevin, alpha Rattus norvegicus

Additional Information